Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX

J A Kanis; H Johansson; E V McCloskey; E Liu; K E Åkesson; F A Anderson; R Azagra; C L Bager; C Beaudart; H A Bischoff-Ferrari; E Biver; O Bruyère; J A Cauley; J R Center; R Chapurlat; C Christiansen; C Cooper; C J Crandall; S R Cummings; J A P da Silva; B Dawson-Hughes; A Diez-Perez; A B Dufour; J A Eisman; P J M Elders; S Ferrari; Y Fujita; S Fujiwara; C-C Glüer; I Goldshtein; D Goltzman; V Gudnason; J Hall; D Hans; M Hoff; R J Hollick; M Huisman; M Iki; S Ish-Shalom; G Jones; M K Karlsson; S Khosla; D P Kiel; W-P Koh; F Koromani; M A Kotowicz; H Kröger; T Kwok; O Lamy; A Langhammer; B Larijani; K Lippuner; D Mellström; T Merlijn; A Nordström; P Nordström; T W O'Neill; B Obermayer-Pietsch; C Ohlsson; E S Orwoll; J A Pasco; F Rivadeneira; A-M Schott; E J Shiroma; K Siggeirsdottir; E M Simonsick; E Sornay-Rendu; R Sund; K M A Swart; P Szulc; J Tamaki; D J Torgerson; N M van Schoor; T P van Staa; J Vila; N J Wareham; N C Wright; N Yoshimura; M C Zillikens; M Zwart; L Vandenput; N C Harvey; M Lorentzon; W D Leslie

doi:10.1007/s00198-023-06870-z

Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX

Osteoporos Int. 2023 Dec;34(12):2027-2045. doi: 10.1007/s00198-023-06870-z. Epub 2023 Aug 11.

Authors

J A Kanis^{1

2}, H Johansson^{3

4}, E V McCloskey^{5

6}, E Liu³, K E Åkesson^{7

8}, F A Anderson⁹, R Azagra^{10

11

12}, C L Bager¹³, C Beaudart^{14

15}, H A Bischoff-Ferrari^{16

17}, E Biver¹⁸, O Bruyère¹⁴, J A Cauley¹⁹, J R Center^{20

21

22}, R Chapurlat²³, C Christiansen¹³, C Cooper^{24

25

26}, C J Crandall²⁷, S R Cummings²⁸, J A P da Silva^{29

30}, B Dawson-Hughes³¹, A Diez-Perez³², A B Dufour^{33

34}, J A Eisman^{20

21

22}, P J M Elders³⁵, S Ferrari¹⁸, Y Fujita³⁶, S Fujiwara³⁷, C-C Glüer³⁸, I Goldshtein^{39

40}, D Goltzman⁴¹, V Gudnason^{42

43}, J Hall⁴⁴, D Hans⁴⁵, M Hoff^{46

47}, R J Hollick⁴⁸, M Huisman^{49

50}, M Iki⁵¹, S Ish-Shalom⁵², G Jones⁵³, M K Karlsson^{7

8}, S Khosla⁵⁴, D P Kiel^{33

34}, W-P Koh^{55

56}, F Koromani^{57

58}, M A Kotowicz^{59

60

61}, H Kröger^{62

63}, T Kwok^{64

65}, O Lamy^{66

67}, A Langhammer⁶⁸, B Larijani⁶⁹, K Lippuner⁷⁰, D Mellström^{71

72}, T Merlijn⁷³, A Nordström^{74

75

76}, P Nordström⁷⁷, T W O'Neill^{78

79}, B Obermayer-Pietsch^{80

81}, C Ohlsson^{82

83}, E S Orwoll⁸⁴, J A Pasco^{59

60

61

85}, F Rivadeneira⁵⁷, A-M Schott⁸⁶, E J Shiroma⁸⁷, K Siggeirsdottir^{42

88}, E M Simonsick⁸⁹, E Sornay-Rendu⁹⁰, R Sund⁶³, K M A Swart^{35

91}, P Szulc⁹⁰, J Tamaki⁹², D J Torgerson⁹³, N M van Schoor⁴⁹, T P van Staa⁹⁴, J Vila⁹⁵, N J Wareham⁹⁶, N C Wright⁹⁷, N Yoshimura⁹⁸, M C Zillikens⁵⁷, M Zwart^{12

99

100

101}, L Vandenput^{3

82}, N C Harvey^{24

25}, M Lorentzon^{3

4}, W D Leslie¹⁰²

Affiliations

¹ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia. [email protected].
² Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. [email protected].
³ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
⁴ Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁵ Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
⁶ MRC Versus Arthritis Centre for Integrated research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK.
⁷ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁸ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
⁹ GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA.
¹⁰ Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
¹¹ Health Centre Badia del Valles, Catalan Institute of Health, Barcelona, Spain.
¹² PRECIOSA-Fundación para la investigación, Barberà del Vallés, Barcelona, Spain.
¹³ Nordic Bioscience A/S, Herlev, Denmark.
¹⁴ WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁵ Department of Health Services Research, University of Maastricht, Maastricht, the Netherlands.
¹⁶ Department of Aging Medicine and Aging Research, University Hospital, Zurich, and University of Zurich, Zurich, Switzerland.
¹⁷ Centre on Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland.
¹⁸ Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁹ Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, USA.
²⁰ Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
²¹ St Vincent's Clinical School, School of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.
²² School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia.
²³ INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital Edouard Herriot, Lyon, France.
²⁴ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
²⁵ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
²⁶ NIHR Oxford Biomedical Research Unit, University of Oxford, Oxford, UK.
²⁷ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
²⁸ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
²⁹ Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁰ Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
³¹ Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
³² Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain.
³³ Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA, USA.
³⁴ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
³⁵ Petra JM Elders Department of General Practice, Amsterdam UMC, location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³⁶ Center for Medical Education and Clinical Training, Kindai University Faculty of Medicine, Osaka, Japan.
³⁷ Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
³⁸ Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany.
³⁹ Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel.
⁴⁰ Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴¹ Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada.
⁴² Icelandic Heart Association, Kopavogur, Iceland.
⁴³ University of Iceland, Reykjavik, Iceland.
⁴⁴ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁵ Interdisciplinary Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital (CHUV) & University of Lausanne, Lausanne, Switzerland.
⁴⁶ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁴⁷ Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.
⁴⁸ Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK.
⁴⁹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
⁵⁰ Department of Sociology, VU University, Amsterdam, The Netherlands.
⁵¹ Department of Public Health, Kindai University Faculty of Medicine, Osaka, Japan.
⁵² Endocrine Clinic, Elisha Hospital, Haifa, Israel.
⁵³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁵⁴ Robert and Arlene Kogod Center on Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.
⁵⁵ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁵⁶ Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
⁵⁷ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁸ Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁹ IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, Victoria, Australia.
⁶⁰ Barwon Health, Geelong, Victoria, Australia.
⁶¹ Department of Medicine -Western Health, The University of Melbourne, St Albans, Victoria, Australia.
⁶² Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
⁶³ Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland.
⁶⁴ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁵ Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
⁶⁶ Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁷ Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁶⁸ HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁶⁹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷⁰ Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷¹ Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷² Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden.
⁷³ Department of General Practice, Amsterdam UMC, location AMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
⁷⁴ School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
⁷⁵ Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
⁷⁶ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁷⁷ Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
⁷⁸ National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁷⁹ Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK.
⁸⁰ Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria.
⁸¹ Center for Biomarker Research in Medicine, Graz, Austria.
⁸² Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁸³ Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁸⁴ Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
⁸⁵ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
⁸⁶ Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France.
⁸⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Baltimore, MD, USA.
⁸⁸ Janus Rehabilitation, Reykjavik, Iceland.
⁸⁹ Translational Gerontology Branch, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
⁹⁰ INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.
⁹¹ PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
⁹² Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁹³ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁹⁴ Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
⁹⁵ Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
⁹⁶ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
⁹⁷ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹⁸ Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan.
⁹⁹ Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain.
¹⁰⁰ Department of Medical Sciences, University of Girona, Girona, Spain.
¹⁰¹ GROIMAP/GROICAP (research groups), Unitat de Suport a la Recerca Girona, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Girona, Spain.
¹⁰² Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.

Introduction: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).

Methods: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients.

Results: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.

Conclusion: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Keywords: Hip fracture; Major osteoporotic fracture; Meta-analysis; Osteoporotic fracture; Prior fracture.

Publication types

Meta-Analysis

MeSH terms

Bone Density
Female
Hip Fractures* / complications
Hip Fractures* / etiology
Humans
Male
Osteoporosis* / complications
Osteoporotic Fractures* / complications
Osteoporotic Fractures* / etiology
Risk Assessment
Risk Factors

Abstract

Publication types

MeSH terms

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